PYM1 is a critical regulator of the exon junction complex (EJC), a multiprotein assembly deposited upstream of exon-exon junctions during pre-mRNA splicing 1. PYM1 functions as an EJC disassembly factor that operates through two distinct mechanisms: it mediates translation-independent EJC destabilization by binding to the EJC core proteins MAGOH-Y14, while the elongating ribosome itself handles translation-dependent removal 2. Additionally, PYM1 bridges the EJC and translation machinery by simultaneously binding the Y14-magoh complex and the 40S ribosomal subunit, enhancing translation of spliced mRNAs 3. PYM1 acts as an EJC specificity factor by limiting non-canonical EJC occupancy, particularly on transcripts with few or long exons, thereby tuning mRNA expression patterns 4. Functionally, PYM1 antagonizes nonsense-mediated decay (NMD) and facilitates EJC protein recycling 1. Disease relevance emerges from flavivirus infection: dengue, West Nile, and Zika viruses exploit PYM1 through capsid-protein interactions to disrupt EJC function and NMD, protecting viral RNA from degradation and enhancing infection 5. This viral hijacking of PYM1 reshapes host mRNA regulation, making PYM1 an antiviral target conserved across multiple flaviviruses.